Protocol Number: 04-NR-0069

Title:

Evaluation of Efficacy and Mechanisms of Topical Thalidomide for Chronic Graft-Versus-Host-Disease Related Stomatitis

Number:

04-NR-0069

Summary:

This study will be conducted in two parts. The first part is a pilot study testing the effects of a thalidomide ointment in patients who have developed oral chronic graft-versus-host-disease (GVHD)-related ulcerative stomatitis following allogeneic bone marrow transplantation (ABMT). Stomatitis is an inflammation of the lining of the throat and mouth that may lead to ulcers and pain in the mouth and throat. GVHD - a condition in which the donor cells see patient's cells as foreign and mount an immune response to them - may be related to increased levels of a substance called TNF-alpha following ABMT. Thalidomide's anti-inflammatory effects may lower TNF-alpha levels and decrease chronic GVHD-related stomatitis and oral pain in these patients.

If this first part of the study is successful, then the second part of the study will be conducted. The second part of this study will test the effects of a thalidomide mouthwash in treating stomatitis in patients who have developed oral chronic graft-versus-host-disease (GVHD)-related stomatitis following allogeneic bone marrow transplantation (ABMT). Applying thalidomide directly to the GVHD-related mouth ulcer in ointment form or to the entire oral cavity by mouthwash form rather than taking it as a pill may reduce the amount of drug that enters the blood stream and cause fewer side effects.

Patients between 18 and 80 years of age who have received an ABMT and developed oral chronic GVHD-related stomatitis as confirmed by surgical biopsy may be eligible for this study. The only eligible female participants for the pilot study will be women who are unable to have children. In the pilot study, participants will be randomly assigned to receive thalidomide ointment or placebo (an ointment with no thalidomide) to use four times a day. In the mouthwash study, participants will be randomly assigned to receive thalidomide mouthwash or placebo (a mouth rinse with no thalidomide) to use four times a day. Participants will also undergo the following procedures before beginning medication, then once a week for 4 weeks, and then approximately 8 weeks after the first visit.

- Interview about current medications and use of alcohol and cigarettes.

- Self-report of mouth and throat pain ratings.

- Dental examination.

- Quality of life questionnaire (The questionnaire is repeated only at week 8 of the study.).

- Mouth photography to measure and record the response to treatment.

- Saliva sampling to look for chemicals, including TNF-alpha.

- Ulcer exudate collected by filter paper to obtain fluid for measuring TNF-alpha levels.

- Gentle swabbing of ulcers to culture for virus, fungus, and bacteria that may be present.

- Small punch biopsy of the area near the ulcer or affected area to check for TNF-alpha (The punch biopsy is repeated only at week 4 of the study.)

- Blood sampling to monitor thalidomide and TNF-alpha levels.

- A urine pregnancy test for women who are able to have children. (The pregnancy test is repeated at weeks 2, 4, and 8.)

Sponsoring Institute:

National Institute of Nursing Research (NINR)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Participating in HSCT or cGVHD protocols and willing to participate in this study concurrently;

Diagnosed with oral cGVHD stomatitis confirmed by surgical biopsy results;

Oral ulceration present

Able to understand and sign protocol informed consent;

Ages 18 to 80 years of age.

EXCLUSION CRITERIA:

Pregnant or lactating females;

For the proof of concept study, females who are not surgically sterilized by means of hysterectomy or tubal ligation;

For the main study, females of childbearing potential who do not agree to the use of two arms of highly effective contraception for at least four weeks prior, during, and for four weeks following the last dose of study drug;

Sexually active males who do not agree to the use of a latex condom while receiving study drug and for four weeks following the last dose of study drug;

Unwilling to follow precautions for use of thalidomide;

Unable to demonstrate appropriate use of study medication;

Concurrent use of non-protocol-related medications confounding assessment of the inflammatory response (antihistamines, non-steroidal anti-inflammatory drugs);

Allergic reaction to thalidomide;

Pre-existing oral infection, which might maximize the possibility of an infection or sepsis contributing to a drug-related adverse event;

Unwilling to forego concurrent treatment for mucosal lesions and/or related oral pain (including topical steroids, viscous lidocaine, topical anti-fungals);

Requiring addition of new systemic therapy including thalidomide, steroids, or radiation therapy;

Use of sedatives (including CNS depressants);

Absolute neutrophil count (ANC) less than 750/mm(3)

Special Instructions:

Currently Not Provided

Keywords:

Stomatitis

Oropharyngeal Pain

TNF-Alpha

Allogeneic BMT

Inflammation

Recruitment Keyword(s):

None

Condition(s):

Graft vs Host Disease

Stomatitis

Bone Marrow Transplantation

Investigational Drug(s):

Thalidomide Gel

Investigational Device(s):

None

Intervention(s):

Drug: Thalidomide

Drug: Thalidomide Gel

Supporting Site:

National Institutes of Nursing Research

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Albandar JM, Brunelle JA, Kingman A. Destructive periodontal disease in adults 30 years of age and older in the United States, 1988-1994. J Periodontol. 1999 Jan;70(1):13-29.

Antin JH, Ferrara JL. Cytokine dysregulation and acute graft-versus-host disease. Blood. 1992 Dec 15;80(12):2964-8.

Aucott DM, Ashley FP. Assessment of the WHO partial recording approach in identification of individuals highly susceptible to periodontitis. Community Dent Oral Epidemiol. 1986 Jun;14(3):152-5.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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